At the present time, no existing antibacterial product provides all features deemed advantageous for such a product. There is continual development of resistance by bacterial strains. A reduction of allergic reactions and of irritation at the site of injection, and greater biological half-life (i.e., longer in vivo activity) are currently desirable features for antibacterial products.
U.S. Pat. No. 4,128,654 issued to Fugitt et al. on Dec. 5, 1978, discloses, among others, compounds of the formula: ##STR1## where A=RS(O).sub.n ;
X=Cl, Br or F; PA1 R=C.sub.1 -C.sub.3 alkyl; and PA1 n=0, 1 or 2. PA1 X=OR.sub.2 (R.sub.2 =H or various acyl moieties). PA1 R.sub.3 represents a phenyl radical which may be substituted by one or more of the following radicals: PA1 Ar is phenyl, optionally substituted by halo or trifluoromethyl; PA1 n is 0 or 1; and PA1 X is --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, an acetylene group or --CH.sub.2 O--. PA1 R.sub.5 is NR.sub.3 R.sub.4 or OR.sub.3 ; PA1 R.sub.6 is alkyl of 1-4 carbons; PA1 R.sub.7 is alkyl of 1-4 carbons, optionally substituted with one or more halogens; PA1 R.sub.8 and R.sub.9 are independently alkyl of 1-4 carbons or, taken together are --(CH.sub.2).sub.p --; PA1 R.sub.10 is H, alkyl of 1-3 carbons, ##STR9## R.sub.11 is alkyl of 1-12 carbons; R.sub.12 is H, alkyl of 1-5 carbons, CH.sub.2 OH or CH.sub.2 SH; PA1 X is Cl, Br or I; PA1 Z is a physiologically acceptable cation; PA1 m is 2 or 3; PA1 n is 0 or 1; and PA1 p is 3, 4 or 5; and PA1 when R.sub.10 is alkyl of 1-3 carbons, R.sub.1 can also be CH.sub.3 S(O).sub.q where q is 0, 1 or 2; PA1 A is ##STR11## of 1 to 8 carbons, optionally substituted with one or more halogen atoms, OH, .dbd.O other than at alpha position, S(O).sub.n R.sub.24, NR.sub.5 R.sub.6, alkenyl of 2-5 carbons, alkynyl of 2-5 carbons or cycloalkyl of 3-8 carbons; PA1 R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ; C.sub.2 -C.sub.4 alkenyl; --NR.sub.9 R.sub.10 ; --N.sub.3 ; ##STR12## --NX.sub.2 ; NR.sub.9 X --.sup.31 NXZ.sup.+ ; R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --; PA1 R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens; PA1 R.sub.5 and R.sub.6 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons; PA1 R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR13## R.sub.8 is H or alkyl of 1-4 carbons; R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl; PA1 R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ; PA1 R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --; PA1 X is Cl, Br or I; PA1 Y is H, F, Cl, Br, alkyl of 1-3 carbons, or NO.sub.2, or A and Y taken together can be --O--(CH.sub.2).sub.t O--; PA1 Z is a physiologically acceptable cation; PA1 n is 0, 1 or 2; PA1 p is 0 or 1; PA1 q is 3, 4 or 5; PA1 r is 4 or 5; PA1 t is 1, 2 or 3; PA1 B is --NH.sub.2, ##STR14## or N.sub.3 ; R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl; PA1 R.sub.13 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms; C.sub.2 -C.sub.4 alkenyl; C.sub.3 -C.sub.4 cycloalkyl; phenyl; --CH.sup.2 OR.sub.15 ; --CH(OR.sub.16)OR.sub.17 ; --CH.sub.2 S(O).sub.v R.sub.14 ; ##STR15## --OR.sub.18 ; --SR.sub.14 ; --CH.sub.2 N.sub.3 ; the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine; --NR.sub.19 R.sub.20 ; or C(NH.sub.2)R.sub.21 R.sub.22 ; PA1 R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms; PA1 R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms; PA1 R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --; PA1 R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl; PA1 R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl; PA1 R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --; PA1 u is 1 or 2; PA1 v is 0, 1 or 2; PA1 m is 2 or 3; PA1 s is 2, 3, 4 or 5; and PA1 R.sub.23 is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, or cycloalkyl of 3-8 carbons; PA1 R.sub.24 is alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons; PA1 R.sub.25 is alkyl of 1-4 carbons substituted with one or more of --S(O).sub.n R.sub.24, --OR.sub.8, ##STR16## --NR.sub.5 R.sub.6, or alkenyl of 2-5 carbons optionally substituted with CHO; or a pharmaceutically suitable salt thereof; provided that: PA1 Ar is an aromatic group selected from the group consisting of ##STR21## diazinyl group optionally substituted with X and Y, a triazinyl group optionally substituted with X and Y, ##STR22## Z is O, S, or NR.sub.5 ; W is CH or N, or also can be S or O when Z is NR.sub.5 ; PA1 X independently is H, --NO.sub.2, --S(O).sub.n R.sub.1, tetrazoyl, ##STR23## of 1 to 8 carbons optionally substituted with one or more halogen atoms, OH, .dbd.O other than at alpha position, S(O).sub.n R.sub.24, or NR.sub.5 R.sub.6, alkenyl of 2-5 carbons or cycloalkyl of 3-8 carbons; PA1 R.sub.1 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms, OH, CN, NR.sub.5 R.sub.6 or CO.sub.2 R.sub.8 ; C.sub.2 -C.sub.4 alkenyl; --NR.sub.9 R.sub.10 ; --N.sub.3 ; ##STR24## --NG.sub.2 ; NR.sub.9 G--.sup.- NGM.sup.+ ; R.sub.2 and R.sub.3 are independently C.sub.1 -C.sub.2 alkyl or, taken together are --(CH.sub.2).sub.q --; PA1 R.sub.4 is alkyl of 1-4 carbons, optionally substituted with one or more halogens; PA1 R.sub.5 and R.sub.6 are independently H, alkyl of 1-8 carbons, cycloalkyl of 3-8 carbons --(CH.sub.2).sub.t OR.sub.8, --(CH.sub.2).sub.t NR.sub.11 R.sub.11a, or --O(CH.sub.2).sub.t NR.sub.11 R.sub.11a ; or taken together are --(CH.sub.2).sub.2 O(CH.sub.2).sub.2 --, --(CH.sub.2).sub.t CH(COR.sub.4)--, or ##STR25## R.sub.7 is --NR.sub.5 R.sub.6, --OR.sub.5 or ##STR26## R.sub.8 is H or alkyl of 1-4 carbons; R.sub.9 is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.8 cycloalkyl; PA1 R.sub.10 is H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.4 cycloalkyl, --OR.sub.8 or --NR.sub.11 R.sub.11A ; PA1 R.sub.11 and R.sub.11A are independently H or C.sub.1 -C.sub.4 alkyl, or taken together, are --(CH.sub.2).sub.r --; PA1 G is Cl, Br or I; PA1 Y independently is H, F, Cl, Br, OR.sub.8, alkyl of 1-3 carbons, or NO.sub.2 ; PA1 X and Y taken together (a) when Ar is ##STR27## to form a fused six-membered carbocyclic ring, or (b) when Ar is ##STR28## M is a physiologically acceptable cation; n is 0, 1 or 2 PA1 p is 0 or 1; PA1 q is 3, 4 or 5; PA1 r is 4 or 5; PA1 t is 1, 2 or 3; PA1 B is --NH.sub.2, ##STR29## or N.sub.3 ; R.sub.12 is H, C.sub.1 -C.sub.10 alkyl or C.sub.3 -C.sub.8 cycloalkyl; PA1 R.sub.13 is H; C.sub.1 -C.sub.4 alkyl optionally substituted with one or more halogen atoms; C.sub.2 -C.sub.4 alkenyl; C.sub.3 -C.sub.4 cycloalkyl; phenyl; --CH.sub.2 OR.sub.15 ; --CH(OR.sub.16)OR.sub.17 ; --CH.sub.2 S(O).sub.v R.sub.14 ; ##STR30## --OR.sub.18 ; --SR.sub.14 ; --CH.sub.2 N.sub.3 ; the aminoalkyl groups derived from .alpha.-amino acids such as glycine, L-alanine, L-cysteine, L-proline, and D-alanine; --NR.sub.19 R.sub.20 ; or --C(NH.sub.2)R.sub.21 R.sub.22 ; PA1 R.sub.14 is C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms; PA1 R.sub.15 is H or C.sub.1 -C.sub.4 alkyl, optionally substituted with one or more halogen atoms; PA1 R.sub.16 and R.sub.17 are independently C.sub.1 -C.sub.4 alkyl or, taken together, are --(CH.sub.2).sub.m --; PA1 R.sub.18 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.11 aralkyl; PA1 R.sub.19 and R.sub.20 are independently H or C.sub.1 -C.sub.2 alkyl; PA1 R.sub.21 and R.sub.22 are independently H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl or, taken together, are --(CH.sub.2).sub.s --; PA1 u is 1 or 2; PA1 v is 0, 1 or 2; PA1 m is 2 or 3; PA1 s is 2, 3, 4 or 5; PA1 R.sub.23 is H, alkyl of 1-8 carbons optionally substituted with one or more halogens, cycloalkyl of 3-8 carbons, alkyl of 1-4 carbons substituted with one or more of --S(O).sub.n R.sub.24, --OR.sub.8, ##STR31## or --NR.sub.5 R.sub.6 ; or alkenyl of 2-5 carbons optionally substituted with CHO or CO.sub.2 R.sub.8 ; PA1 R.sub.24 is alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons; and PA1 R.sub.25 is R.sub.6 or NR.sub.5 R.sub.6 ; PA1 1) when B is NH.sub.2, then Ar is not phenyl optionally substituted with halogen or CF.sub.3.
The compounds are disclosed as being useful in controlling fungal and bacterial diseases of plants.
Reissue U.S. Pat. No. 29,607 reissued Apr. 11, 1978 discloses derivatives of 5-hydroxymethyl-3-substituted-2-oxazolidinones of the formula: ##STR2## where R is H, F, CH.sub.3, or CF.sub.3. Such compounds are described as having antidepressive, tranquilizing, sedative, and antiinflammatory properties.
U.S. Pat. No. 4,250,318, which was issued on Feb. 10, 1981, discloses antidepressant compounds of the formula: ##STR3## where R' can be, among others, a para-n-pentylamino group, an SR.sub.1 group where R.sub.1 is C.sub.1 -C.sub.5 alkyl, or an acetylmethylthio group.
U.S. Pat. No. 4,340,606, issued to Fugitt et al. on Jul. 20, 1982, discloses antibacterial agents of the general formula: ##STR4## where R.sub.1 =CH.sub.3, C.sub.2 H.sub.5, CF.sub.2 H, CF.sub.3 or CF.sub.2 CF.sub.2 H; and
U.S. Pat. No. 3,687,965, issued to Fauran et al. on Aug. 29, 1972, discloses compounds of the formula: ##STR5## where --N(R.sub.1)(R.sub.2) represents either dialkylamino radical in which the alkyl portions have one to five carbon atoms, or a heterocyclic amino radical which may be substituted by an alkyl radical having one to five carbon atoms or by a pyrrolidinocarbonylmethyl radical, and
an alkoxy radical having one to five carbon atoms; PA2 a halogen atom; PA2 a trifluoromethyl radical, or PA2 a carboxyl radical which may be esterified. PA2 1) when A is CH.sub.3 S--, then B is not ##STR17## 2) when A is CH.sub.3 SO.sub.2 --, then B is not ##STR18## 3) when A is H.sub.2 NSO.sub.2 -- and B is ##STR19## then R.sub.12 is H; 4) when A is --CN, B is not --N.sub.3 ; PA2 5) when A is (CH.sub.3).sub.2 CH, B is not NHCOCH.sub.2 Cl; PA2 6) when A is OR.sub.5, then B is not NH.sub.2 ; PA2 7) when A is F, then B is not NHCO.sub.2 CH.sub.3.
The patent states that these compounds possess hypotensive, vasodilatatory, spasmolytic, sedative, myorelaxant, analgesic and antiinflammatory properties. There is no mention of antibacterial properties.
Belgian Patent 892,270, published Aug. 25, 1982, discloses monoamine oxidase inhibitors of the formula ##STR6## where R is H, C.sub.1 -C.sub.4 alkyl or propargyl;
U.S. Pat. No. 4,461,773 issued to W. A. Gregory on Jul. 24, 1984 discloses antibacterial agents of the formula ##STR7## wherein, for the l, and mixtures of the d and l stereoisomers of the compound, ##STR8## R.sub.3 and R.sub.4 are independently H, alkyl of 1-4 carbons or cycloalkyl of 3-8 carbons;
or a pharmaceutically acceptable salt thereof.
U.S. Pat. No. 4,705,799 issued to Gregory on Nov. 10, 1987 discloses antibacterial agents of the formula: ##STR10## wherein, for the l, and mixtures of the d and l stereoisomers of the compound,
None of the above-mentioned references suggest the novel antibacterial compounds of this invention.